|
1
|
Jalihal U, Mahapatra JR, Kumar A, Bharadwaj T, Singh HD, Mehta V, Patil DR, Swami OC. Comparative Efficacy of Dexlansoprazole, Pantoprazole, Esomeprazole, and Rabeprazole in Achieving Optimal 24-Hour Intragastric pH Control: A Randomized Crossover Study Using Ambulatory pH Monitoring. Cureus 2024; 16:e71418. [PMID: 39539895 PMCID: PMC11558283 DOI: 10.7759/cureus.71418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2024] [Indexed: 11/16/2024] Open
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) regulate gastric acid reflux. Dexlansoprazole's efficacy in prolonging acid suppression compared to conventional PPIs and placebo requires evaluation. METHODS A prospective, randomized, placebo-controlled, five-way crossover pilot study was conducted on healthy volunteers comparing the potency of dexlansoprazole to conventional PPIs in which five patients were randomized into five treatment cohorts, including dexlansoprazole 60 mg, pantoprazole 40 mg, esomeprazole 40 mg, rabeprazole 20 mg, and placebo, assessing 24-hour intragastric pH using Z/pH Recorder (ZepHr®, Diversatek, Inc., Milwaukee, WI) and analyzing statistical differences via paired t-test. RESULTS Dexlansoprazole showed significantly longer durations with pH > 4.0 compared to placebo (P < 0.001) and all other PPIs (P < 0.05) over 24 hours. Although not significant in the first 0-12-hour period, dexlansoprazole maintained significantly higher pH levels in the last 12-24-hour period compared to pantoprazole (P = 0.001) and esomeprazole (P = 0.044) but not with rabeprazole (P = 0.075). Additionally, during the 24-hour pH monitoring measured at 30-minute intervals, dexlansoprazole (mean pH = 3.98 ± 0.11) consistently showed higher values than pantoprazole (mean pH = 3.48 ± 0.12), rabeprazole (mean pH = 3.66 ± 0.05), esomeprazole (mean pH = 3.66 ± 0.05), and placebo (mean pH = 2.52 ± 0.12), indicating its superior potency. CONCLUSION Dexlansoprazole's dual-delayed release mechanism demonstrates superior acid suppression compared to traditional PPIs and placebo in this pilot study. Larger studies are needed to further evaluate its long-term efficacy and safety.
Collapse
Affiliation(s)
- Umesh Jalihal
- Gastroenterology, Karnataka Gastro Centre, Bengaluru, IND
| | | | - Ajit Kumar
- Gastroenterology, KIMS Hospital, Hyderabad, IND
| | | | - Harsh D Singh
- Gastroenterology, Sukhbir Hospital, Amritsar, IND
- Gastroenterology, Ivy Hospital, Amritsar, IND
| | - Vatsal Mehta
- Gastroenterology, Health1 Super Speciality Hospital, Ahmedabad, IND
| | - Dinesh R Patil
- Clinical Pharmacology, Alembic Pharmaceuticals Ltd, Mumbai, IND
| | - Onkar C Swami
- Gastroenterology and Clinical Pharmacology, Alembic Pharmaceuticals Ltd, Mumbai, IND
| |
Collapse
|
|
2
|
Lim H, Park JK, Chung H, Lee SH, Park JM, Park JH, Kim GH, Shin SK, Hong SJ, Lee KJ, Park MI, Jung HK, Kim HS, Sung JK, Jeon SW, Choi SC, Moon JS, Kim N, Park JJ, Hong SH, Kim NY, Jung HY. Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study. BMC Gastroenterol 2023; 23:447. [PMID: 38110901 PMCID: PMC10729464 DOI: 10.1186/s12876-023-03087-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 12/10/2023] [Indexed: 12/20/2023] Open
Abstract
BACKGROUND Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION NCT04080726 ( https://classic. CLINICALTRIALS gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.
Collapse
Affiliation(s)
- Hyun Lim
- Department of Internal Medicine, University of Hallym College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea
| | - Jong Kyu Park
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, Republic of Korea
| | - Hyunsoo Chung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Si Hyung Lee
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea
| | - Jae Myung Park
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung Ho Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Republic of Korea
| | - Sung Kwan Shin
- Division of Gastroenterology, Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Republic of Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Republic of Korea
| | - Hyun-Soo Kim
- Department of internal medicine, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Jae Kyu Sung
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Seong Woo Jeon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Suck Chei Choi
- Department of Gastroenterology, Digestive Disease Research Institute, Wonkwang University Hospital, Iksan, Republic of Korea
| | - Jeong Seop Moon
- Department of Internal Medicine, Inje University College of Medicine, Seoul, Republic of Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jong-Jae Park
- Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Guro Hospital, Seoul, Republic of Korea
| | - Sung Hee Hong
- Hanmi Pharmaceutical Co., Ltd, Seoul, Republic of Korea
| | - Na Young Kim
- Hanmi Pharmaceutical Co., Ltd, Seoul, Republic of Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
| |
Collapse
|
|
3
|
Han S, Choi HY, Kim YH, Choi S, Kim S, Nam JY, Kim B, Song GS, Lim HS, Bae KS. Comparison of Pharmacodynamics between Tegoprazan and Dexlansoprazole Regarding Nocturnal Acid Breakthrough: A Randomized Crossover Study. Gut Liver 2023; 17:92-99. [PMID: 36317518 PMCID: PMC9840922 DOI: 10.5009/gnl220050] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 06/17/2022] [Accepted: 06/29/2022] [Indexed: 01/14/2023] Open
Abstract
Background/Aims Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects. Methods In a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation. Results All 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration-time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing. Conclusions All the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.
Collapse
Affiliation(s)
- Sungpil Han
- Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hee Youn Choi
- Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yo Han Kim
- Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - SeungChan Choi
- Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seokuee Kim
- Clinical Development, HK inno.N Corp., Seoul, Korea
| | - Ji Yeon Nam
- Clinical Development, HK inno.N Corp., Seoul, Korea
| | - Bongtae Kim
- Clinical Development, HK inno.N Corp., Seoul, Korea
| | | | - Hyeong-Seok Lim
- Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyun-Seop Bae
- Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea,Corresponding AuthorKyun-Seop Bae, ORCIDhttps://orcid.org/0000-0001-7399-5879, E-mail
| |
Collapse
|
|
4
|
Dai R, Sag AA, Martin JG, Befera NT, Pabon-Ramos WM, Suhocki PV, Smith TP, Kim CY, Muir AJ, Ronald J. Proton pump inhibitor use is associated with increased rates of post-TIPS hepatic encephalopathy: Replication in an independent patient cohort. Clin Imaging 2021; 77:187-192. [PMID: 33940357 DOI: 10.1016/j.clinimag.2021.04.034] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 04/18/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Proton pump inhibitor (PPI) use is a potential risk factor for hepatic encephalopathy (HE), but few studies have examined the effect on post-TIPS HE. The purpose of this study was to determine whether PPIs are associated with increased rates of post-TIPS HE in an independent patient cohort. MATERIALS AND METHODS This single-institution retrospective study analyzed 86 patients (54 male, mean age 58.2) following TIPS from 1/1/2017 to 12/31/2019. Dates of PPI usage and episodes of new or worsening HE were recorded. Poisson regression with generalized estimating equations was used to test for association between PPI use and post-TIPS HE and to test for dose dependence. Post-TIPS HE was also analyzed using the Andersen-Gill survival model for recurrent events. RESULTS There were 1.88 episodes of new or worsening post-TIPS HE per person-year among 35 patients on uninterrupted PPIs therapy, 1.95 on PPIs and 0.94 off PPIs among 35 patients on intermittent therapy, and 0.47 among 16 patients never on PPIs. PPI use was significantly associated with post-TIPS HE in both univariable (incidence rate ratio (IRR) = 2.62; CI = 1.41-4.84; p = 0.002) and multivariable (IRR = 2.31; CI = 1.37-3.89; p = 0.002) regression. Analysis of only those patients on PPIs showed increased rates of HE with higher doses (IRR = 1.17 per 10 mg omeprazole equivalent; CI = 1.04-1.33; p = 0.011). Recurrent events survival analysis supported the association between PPI use and HE in univariable (hazard ratio (HR) = 2.17; CI = 1.19-3.95; p = 0.011) and multivariable (HR = 1.87; CI = 1.12-3.13; p = 0.017) analysis. CONCLUSION In an independent patient cohort PPI use was associated with increased rates of new or worsening post-TIPS HE.
Collapse
Affiliation(s)
- Rui Dai
- Duke University School of Medicine, DUMC 3710, Durham, NC 27710, USA
| | - Alan A Sag
- Division of Vascular & Interventional Radiology, Department of Radiology, Duke University Medical Center, DUMC 3808, Durham, NC 27710, USA
| | - Jonathan G Martin
- Division of Vascular & Interventional Radiology, Department of Radiology, Duke University Medical Center, DUMC 3808, Durham, NC 27710, USA
| | - Nicholas T Befera
- Division of Vascular & Interventional Radiology, Department of Radiology, Duke University Medical Center, DUMC 3808, Durham, NC 27710, USA
| | - Waleska M Pabon-Ramos
- Division of Vascular & Interventional Radiology, Department of Radiology, Duke University Medical Center, DUMC 3808, Durham, NC 27710, USA
| | - Paul V Suhocki
- Division of Vascular & Interventional Radiology, Department of Radiology, Duke University Medical Center, DUMC 3808, Durham, NC 27710, USA
| | - Tony P Smith
- Division of Vascular & Interventional Radiology, Department of Radiology, Duke University Medical Center, DUMC 3808, Durham, NC 27710, USA
| | - Charles Y Kim
- Division of Vascular & Interventional Radiology, Department of Radiology, Duke University Medical Center, DUMC 3808, Durham, NC 27710, USA
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University Medical Center, DUMC 3913, Durham, NC 27710, USA
| | - James Ronald
- Division of Vascular & Interventional Radiology, Department of Radiology, Duke University Medical Center, DUMC 3808, Durham, NC 27710, USA.
| |
Collapse
|
|
5
|
Lin XH, Luo JC, Ting PH, Chang TE, Huang YH, Hou MC, Lee FY. Comparison of the efficiency of two different proton pump inhibitor formula in treatment of patients with atypical gastroesophageal reflux disease: a prospective randomized study. J Gastroenterol Hepatol 2020; 35:2096-2102. [PMID: 32401385 DOI: 10.1111/jgh.15093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 05/02/2020] [Accepted: 05/07/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM The prospective, open-label, randomized study aims to compare the efficacy of lansoprazole, a fast orally disintegrating proton pump inhibitor (PPI), and dexlansoprazole, a dual delayed release PPI, in patients with atypical symptoms of gastroesophageal reflux disease (GERD). METHODS Patients with atypical GERD symptoms with a total reflux symptom index score > 10 were eligible for enrollment. From February 2018 to December 2019, 232 subjects were randomly assigned (1:1 ratio) to receive oral lansoprazole, Takepron OD 30 mg, once daily before breakfast or oral dexlansoprazole, Dexilant 60 mg, once daily before breakfast for 8 weeks. The primary end-point is to compare the symptoms response rate after an 8-week PPI therapy between the two groups. RESULTS There were 232 study subjects enrolling in this study. After the 8-week PPI therapy, dexlansoprazole-treated group had a significantly higher response rate than lansoprazole-treated group in cough (76.5% vs 38.0%) and globus (69.7% vs 30.8%) (P all < 0.05 by intention-to-treat). Multivariate logistic regression analysis showed that the use of dexlansoprazole, presence of dyslipidemia, and typical GERD symptoms (acid reflux and heartburn) were predictors for symptom response for cough; the use of dexlansoprazole and presence of erosive esophagitis were predictors for symptom response for globus (P all < 0.05). No predictor for therapy response to hoarseness was noted. CONCLUSIONS There is a higher response rate for cough and globus symptoms in patients with atypical GERD after the 8-week PPI therapy with dexlansoprazole rather than lansoprazole.
Collapse
Affiliation(s)
- Xi-Hsuan Lin
- Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan
| | - Jiing-Chyuan Luo
- Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Keelung Hospital, Ministry of Health and Welfare, Keelung, Taiwan
| | - Po-Hsiang Ting
- Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Tien-En Chang
- Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ming-Chih Hou
- Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Fa-Yauh Lee
- Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| |
Collapse
|
|
6
|
Ryan P, Odunayo A, Price J, Hecht S, Hillsman S, Galyon G, Steiner J, Tolbert MK. Comparative analysis of the effect of PO administered acid suppressants on gastric pH in healthy cats. J Vet Intern Med 2020; 34:1879-1885. [PMID: 32885499 PMCID: PMC7517516 DOI: 10.1111/jvim.15887] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 08/05/2020] [Accepted: 08/18/2020] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are among the most commonly prescribed medications for esophagitis and upper gastrointestinal erosion and ulceration in cats. Newer PPIs such as lansoprazole and esomeprazole are believed to be effective in cats, but the effect of many of these PPIs on gastric pH in cats has not been explored. HYPOTHESIS/OBJECTIVES To evaluate the efficacy of PO esomeprazole, dexlansoprazole, and lansoprazole on intragastric pH in healthy cats. We hypothesized that esomeprazole and lansoprazole would provide superior acid suppression compared to dexlansoprazole and reach pH goals extrapolated from people for the treatment of esophagitis and duodenal ulceration. ANIMALS Twelve healthy research cats. METHODS Randomized, 3-way crossover study. Cats were given esomeprazole and lansoprazole at a dosage of 1 mg/kg PO q12h or dexlansoprazole at 6 mg/kg PO q12h. Intragastric pH was recorded at baseline and for 4 days of treatment. Mean pH and the mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were compared among and within treatment groups. RESULTS Cats treated with lansoprazole had a lower MPT ± SD of intragastric pH ≥3 (8.8 ± 6.8%) and mean ± SD pH (1.6 ± 0.5) than did cats treated with dexlansoprazole (41.2 ± 34.6% and 3.11 ± 1.6, respectively) or esomeprazole (54 ± 33.8% and 4.1 ± 3.9, respectively;P ≤ .04). Esomeprazole was the only treatment that achieved the goals defined for people for the treatment of duodenal ulceration by Day 4 of treatment (MPT ± SD of intragastric pH ≥4 of 77.1 ± 29.2%). CONCLUSIONS AND CLINICAL IMPORTANCE Orally administered esomeprazole might be a superior acid suppressant in cats compared to PO lansoprazole or dexlansoprazole.
Collapse
Affiliation(s)
- Phillip Ryan
- Department of Small Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee, USA
| | - Adesola Odunayo
- Department of Small Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee, USA
| | - Josh Price
- Department of Small Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee, USA
| | - Silke Hecht
- Department of Small Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee, USA
| | - Shanna Hillsman
- Department of Small Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee, USA
| | - Gina Galyon
- Department of Small Animal Clinical Sciences, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee, USA
| | - Joerg Steiner
- Department of Small Animal Clinical Sciences, Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, College Station, Texas, USA
| | - M Katherine Tolbert
- Department of Small Animal Clinical Sciences, Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, College Station, Texas, USA
| |
Collapse
|
|
7
|
Tai WC, Liang CM, Bi KW, Kuo CM, Lu LS, Wu CK, Yang SC, Kuo YH, Lee CH, Huang CF, Hsu CN, Hsu PI, Wu DC, Hu TH, Wu KL, Chuah SK. A comparison between dexlansoprazole modified release-based and lansoprazole-based nonbismuth quadruple (concomitant) therapy for first-line Helicobacter pylori eradication: a prospective randomized trial. Infect Drug Resist 2019; 12:2923-2931. [PMID: 31571945 PMCID: PMC6754331 DOI: 10.2147/idr.s213998] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 09/03/2019] [Indexed: 01/10/2023] Open
Abstract
PURPOSE Steadily maintaining high intra-gastric PH is the major factor for successful Helicobacter pylori (H.pylori) eradication. It is important to search for a stronger PPI. Dexlansoprazole MR is a dual delayed release formulation PPI taken once daily which is capable of maintaining longer duration of high intra-gastric PH. It is very effective in treating gastroesophageal disease but reports on H, pylori eradication is very rare. This study sought to compare dexlansoprazole MR-based concomitant treatment and lansoprazole-based concomitant treatment in H. pylori infection and to investigate the factors that affect the eradication rates. METHODS Two hundred two participants with H. pylori infection were included and randomly assigned to seven days of dexlansoprazole MR-based concomitant therapy (dexlansoprazole MR 60 mg once daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily; DACM group) or a seven days of lansoprazole-based concomitant therapy (lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, and metronidazole 500 mg twice daily; LACM group). The participants were asked to perform urea breath tests eight weeks later. RESULTS The eradication rates in the DACM group were 86.1% [95% confidence interval (CI): 77.8%-92.2%] in the ITT analysis and 90.6% (95% CI: 82.9%-95.6%) in the PP analysis, respectively, as compared with 90.1% (95% CI: 82.6%-95.2%) and 92.6% (95% CI: 85.5%-96.9%) (p=0.384 and p=0.572, respectively) in the LACM group for the same analyses. The adverse event rates were 11.5% in the DACM group and 10.2% in the LACM group (p=0.779). CONCLUSION As a first-line H. pylori treatment regimen, dexlansoprazole MR-based concomitant therapy attained a successful eradication rate of 90%, which was non inferior to that of lansoprazole-based concomitant treatment. CLINICALTRIALSGOV IDENTIFIER NCT03829150.
Collapse
Affiliation(s)
- Wei-Chen Tai
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Ming Liang
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Kuo-Wei Bi
- Division of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chung-Mou Kuo
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Lung-Sheng Lu
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Cheng-Kun Wu
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Shih-Cheng Yang
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yuan-Hung Kuo
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chen-Hsiang Lee
- Division of Infectious Diseases, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Fang Huang
- Division of Family Physician, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Pin-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, National Yang-Ming University, Kaohsiung, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Chang Gung University College of Medicine, Taoyuan City, Taiwan
| | - Keng-Liang Wu
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Chang Gung University College of Medicine, Taoyuan City, Taiwan
| | - Seng-Kee Chuah
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Chang Gung University College of Medicine, Taoyuan City, Taiwan
| |
Collapse
|
|
8
|
Maev IV, Selskaya JV, Andreev DN, Dicheva DT, Bogolepova ZN, Kuznetsova EI. Laryngopharyngeal reflux: clinical significance, modern approaches to diagnosis and treatment. MEDICAL COUNCIL 2019:8-16. [DOI: 10.21518/2079-701x-2019-3-8-16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Gastroesophageal reflux disease (GERD) is one of the most common pathologies in modern clinical practice. Laryngopharyngeal reflux (LPR) is considered to be an extraesophageal manifestation of GERD and is characterized by retrograde ingestion of gastric content into the larynx and pharynx, leading to recurrent otolaryngological symptoms. Classical manifestations of LPR are hoarseness, perspiration, dryness and feeling of lump in the throat, coughing. There is no «gold standard» for the diagnosis of LPR. At the same time, several instrumental methods are used in clinical practice to verify the diagnosis: laryngoscopy and EGDS are the most common, and in some cases - 24-hour pH-metry and impedancemetry. In the case of an established diagnosis of LPR, it is recommended to use a standard dosage of PPI twice a day for 3–6 months.
Collapse
Affiliation(s)
- I. V. Maev
- Federal State Budgetary Educational Institution of the Higher Education «Moscow State University of Medicine and Dentistry named after A.I. Yevdokimov» of the Ministry of Healthcare of the Russian Federation
| | | | - D. N. Andreev
- Federal State Budgetary Educational Institution of the Higher Education «Moscow State University of Medicine and Dentistry named after A.I. Yevdokimov» of the Ministry of Healthcare of the Russian Federation
| | - D. T. Dicheva
- Federal State Budgetary Educational Institution of the Higher Education «Moscow State University of Medicine and Dentistry named after A.I. Yevdokimov» of the Ministry of Healthcare of the Russian Federation; European Medical Center Joint Stock Company
| | | | - E. I. Kuznetsova
- Federal State Budgetary Educational Institution of the Higher Education «Moscow State University of Medicine and Dentistry named after A.I. Yevdokimov» of the Ministry of Healthcare of the Russian Federation
| |
Collapse
|
|
9
|
Chiang HH, Wu DC, Hsu PI, Kuo CH, Tai WC, Yang SC, Wu KL, Yao CC, Tsai CE, Liang CM, Wang YK, Wang JW, Huang CF, Chuah SK. Clinical efficacy of 60-mg dexlansoprazole and 40-mg esomeprazole after 24 weeks for the on-demand treatment of gastroesophageal reflux disease grades A and B: a prospective randomized trial. Drug Des Devel Ther 2019; 13:1347-1356. [PMID: 31118571 PMCID: PMC6499145 DOI: 10.2147/dddt.s193559] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 03/12/2019] [Indexed: 12/22/2022] Open
Abstract
Purpose: Research comparing the clinical efficacy of dexlansoprazole and esomeprazole has been limited. This study aims to compare the clinical efficacy of single doses of dexlansoprazole (modified-release 60 mg) and esomeprazole (40 mg) after 24-week follow-up in patients with mild erosive esophagitis. Methods: We enrolled 86 adult GERD subjects, randomized in a 1:1 ratio to two sequence groups defining the order in which they received single doses of dexlansoprazole (n=43) and esomeprazole (n=43) for 8 weeks as initial treatment. Patients displaying complete symptom resolution (CSR) by the end of initial treatment (8 weeks) were switched to on-demand therapy until the end of 24 weeks. Follow-up endoscopy was performed either at the end of 24 weeks or when severe reflux symptoms occurred. Five patients were lost to follow-up, leaving 81 patients (dexlansoprazole, n=41; esomeprazole, n=40) in the per-protocol analysis. Results: The GERDQ scores at 4-, 8-, 12-, 16-, 20-, and 24-week posttreatment were less than the baseline score. The CSR, rate of symptom relapse, days to symptom resolution, sustained healing rate of erosive esophagitis, treatment failure rate, and the number of tablets taken in 24 weeks were similar in both groups. The esomeprazole group had more days with reflux symptoms than the dexlansoprazole group (37.3±37.8 vs 53.9±54.2; P=0.008). In the dexlansoprazole group, patients exhibited persistent improvement in the GERDQ score during the on-demand period (week 8 vs week 24; P<0.001) but not in the esomeprazole group (week 8 vs week 24; P=0.846). Conclusions: This study suggests that the symptom relief effect for GERD after 24 weeks was similar for dexlansoprazole and esomeprazole. Dexlansoprazole exhibited fewer days with reflux symptoms in the 24-week study period, with better persistent improvement in the GERDQ score in the on-demand period. (ClinicalTrials. gov number: NCT03128736).
Collapse
Affiliation(s)
- Hung-Hsien Chiang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pin-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, National Yang-Ming University, Kaohsiung, Taiwan
| | - Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Chen Tai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Shih-Cheng Yang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Keng-Liang Wu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Chien Yao
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-En Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Ming Liang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yao-Kuang Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jiunn-Wei Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Fang Huang
- Division of Family Physicians, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Seng-Kee Chuah
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - on behalf of the Taiwan Acid-Related Disease Study Group
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, National Yang-Ming University, Kaohsiung, Taiwan
- Division of Family Physicians, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| |
Collapse
|
|
10
|
Proton Pump Inhibitor Use Is Associated with an Increased Frequency of New or Worsening Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Creation. J Vasc Interv Radiol 2019; 30:163-169. [PMID: 30638914 DOI: 10.1016/j.jvir.2018.10.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 10/10/2018] [Accepted: 10/13/2018] [Indexed: 12/22/2022] Open
|
|
11
|
Kukulka M, Nudurupati S, Perez MC. Bioavailability of dexlansoprazole delayed-release capsule granules when administered via nasogastric tube or orally via syringe. Clin Exp Gastroenterol 2018; 11:381-389. [PMID: 30323643 PMCID: PMC6177519 DOI: 10.2147/ceg.s138580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Objective To assess the effect of route of administration on the bioavailability of dexlansoprazole 60 mg delayed-release capsule granules. Methods One open-label, Phase I, single-dose, 3-period crossover study was conducted in healthy adults. The bioavailability of Dexilant® (dexlansoprazole) after dexlansoprazole capsule granules were mixed with water and administered via 16 French nasogastric tube or orally via syringe was compared to administration of the intact capsule in the fasted state, swallowed with water. Blood samples were collected before and after dosing to determine dexlansoprazole pharmacokinetic parameter estimates and plasma concentrations. Results Similar values for area under the plasma concentration-time curve and observed maximum plasma concentration were achieved when the dexlansoprazole 60 mg capsule was administered as the intact capsule or when the granules were mixed with water and administered via nasogastric tube or orally via syringe. The primary endpoints of maximum plasma concentration and area under the plasma concentration-time curve demonstrated bioequivalence when assessing these alternative routes of administration. Most adverse events were rated as mild and were comparable irrespective of administration route. Conclusion Systemic exposure to dexlansoprazole was equivalent regardless of administration route. The dexlansoprazole capsule was well tolerated.
Collapse
Affiliation(s)
- Michael Kukulka
- Department of Clinical Pharmacology, Takeda Development Center Americas, Inc., Deerfield, IL, USA
| | - Sai Nudurupati
- Department of Analytical Sciences, Takeda Development Center Americas, Inc., Deerfield, IL, USA
| | - Maria Claudia Perez
- Department of Clinical Science, Takeda Development Center Americas, Inc., Deerfield, IL, USA,
| |
Collapse
|
|
12
|
Luo L, Wen X, Du Y, Jiang Z, Guo X. Enantioselective analysis of lansoprazole in rat plasma by LC-MS/MS: Application to a stereoselective pharmacokinetic study. Biomed Chromatogr 2018; 32:e4345. [DOI: 10.1002/bmc.4345] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 07/06/2018] [Accepted: 07/11/2018] [Indexed: 11/10/2022]
Affiliation(s)
- Linda Luo
- School of Pharmacy; Shenyang Pharmaceutical University; Shenyang Liaoning Province People's Republic of China
| | - Xiaoli Wen
- School of Pharmacy; Shenyang Pharmaceutical University; Shenyang Liaoning Province People's Republic of China
| | - Yueying Du
- School of Pharmacy; Shenyang Pharmaceutical University; Shenyang Liaoning Province People's Republic of China
| | - Zhen Jiang
- School of Pharmacy; Shenyang Pharmaceutical University; Shenyang Liaoning Province People's Republic of China
| | - Xingjie Guo
- School of Pharmacy; Shenyang Pharmaceutical University; Shenyang Liaoning Province People's Republic of China
| |
Collapse
|
|
13
|
Stern EK, Carlson DA, Falmagne S, Hoffmann AD, Carns M, Pandolfino JE, Hinchcliff M, Brenner DM. Abnormal esophageal acid exposure on high-dose proton pump inhibitor therapy is common in systemic sclerosis patients. Neurogastroenterol Motil 2018; 30:10.1111/nmo.13247. [PMID: 29110377 PMCID: PMC5771836 DOI: 10.1111/nmo.13247] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 10/09/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Esophageal dysfunction and gastro-esophageal reflux disease (GERD) are common among patients with systemic sclerosis (SSc). Although high-dose proton pump inhibitors (PPIs) typically normalize esophageal acid exposure, the effectiveness of PPI therapy has not been systematically studied in SSc patients. The aim of this study was to characterize reflux in SSc patients on high-dose PPI using esophageal pH-impedance testing. METHODS In this case-controlled retrospective analysis, 38 patients fulfilling 2013 American College of Rheumatology SSc criteria who underwent esophageal pH-impedance testing on twice-daily PPI between January 2014 and March 2017 at a tertiary referral center were compared with a control-cohort of 38 non-SSc patients matched for PPI formulation and dose, hiatal hernia size, age, and gender. Patient clinical characteristics, including endoscopy and high-resolution manometry findings, were assessed via chart review. KEY RESULTS On pH-impedance, SSc patients had higher acid exposure times (AETs) than controls. Sixty-one percent of the SSc patients and 18% of the control patients had a total AET ≥4.5% (P < .001). Systemic sclerosis patients also had significantly longer AETs, longer median bolus clearance, and lower nocturnal impedance values. CONCLUSIONS & INFERENCES Abnormal esophageal acid exposure despite high-dose PPI therapy was common among patients with SSc. The lack of increased reflux episodes in the SSc patients, and longer bolus clearance times and lower nocturnal impedance, supports ineffective clearance as the potential mechanism. Systemic sclerosis patients may require adjunctive therapies to PPIs to control acid reflux.
Collapse
Affiliation(s)
- Emily K. Stern
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Dustin A. Carlson
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Sophia Falmagne
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Aileen D. Hoffmann
- Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Mary Carns
- Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - John E. Pandolfino
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Monique Hinchcliff
- Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Darren M. Brenner
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| |
Collapse
|
|
14
|
The role of pH in symptomatic relief and effective treatment of gastroesophageal reflux disease. GASTROENTEROLOGY REVIEW 2018; 12:244-249. [PMID: 29358992 PMCID: PMC5771447 DOI: 10.5114/pg.2017.72097] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Accepted: 11/20/2017] [Indexed: 12/22/2022]
Abstract
Gastroesophageal reflux disease (GERD) is a condition in which gastroduodenal contents pass into the oesophagus and cause troublesome symptoms and complications. The aetiopathogenesis of gastroesophageal reflux disease is complex and multifactorial. Acid reflux plays an important role in the GERD pathogenesis, both in erosive and non-erosive reflux disease. Reduction of GERD symptoms and mucosal healing correlates with the number of hours that intragastric acid is suppressed to a pH > 4.0. Mucosal healing was achieved in most of patients who received different types of proton pump inhibitors, but only in 50% of those who received H2 blockers. These findings seem to be best accounted for by differences in the duration and degree of acid suppression achieved by different classes of drugs and perhaps between agents within those classes.
Collapse
|
|
15
|
Liang CM, Kuo MT, Hsu PI, Kuo CH, Tai WC, Yang SC, Wu KL, Wang HM, Yao CC, Tsai CE, Wang YK, Wang JW, Huang CF, Wu DC, Chuah SK. First-week clinical responses to dexlansoprazole 60 mg and esomeprazole 40 mg for the treatment of grades A and B gastroesophageal reflux disease. World J Gastroenterol 2017; 23:8395-8404. [PMID: 29307999 PMCID: PMC5743510 DOI: 10.3748/wjg.v23.i47.8395] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 09/19/2017] [Accepted: 09/26/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To compare the one-week clinical effects of single doses of dexlansoprazole and esomeprazole on grades A and B erosive esophagitis. METHODS We enrolled 175 adult patients with gastroesophageal reflux disease (GERD). The patients were randomized in a 1:1 ratio into two sequence groups to define the order in which they received single doses of dexlansoprazole (n = 88) and esomeprazole (n = 87) for an intention-to-treat analysis. The primary end-points were the complete symptom resolution (CSR) rates at days 1, 3, and 7 after drug administration. RESULTS Thirteen patients were lost to follow-up, resulting in 81 patients in each group for the per-protocol analysis. The CSRs for both groups were similar at days 1, 3 and 7. In the subgroup analysis, the female patients achieved higher CSRs in the dexlansoprazole group than in the esomeprazole group at day 3 (38.3% vs 18.4%, P = 0.046). An increasing trend toward a higher CSR was observed in the dexlansoprazole group at day 7 (55.3% vs 36.8%, P = 0.09). In the esomeprazole group, female sex was a negative predictive factor for CSR on post-administration day 1 [OR = -1.249 ± 0.543; 95%CI: 0.287 (0.099-0.832), P = 0.022] and day 3 [OR = -1.254 ± 0.519; 95%CI: 0.285 (0.103-0.789), P = 0.016]. Patients with spicy food eating habits achieved lower CSRs on day 1 [37.3% vs 21.4%, OR = -0.969 ± 0.438; 95%CI: 0.380 (0.161-0.896), P = 0.027]. CONCLUSION The overall CSR for GERD patients was similar at days 1-7 for both the dexlansoprazole and esomeprazole groups, although a higher incidence of CSR was observed on day 3 in female patients who received a single dose of dexlansoprazole.
Collapse
Affiliation(s)
- Chih-Ming Liang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Ming-Te Kuo
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Pin-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, National Yang-Ming University, Kaohsiung 833, Taiwan
| | - Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung 833, Taiwan
| | - Wei-Chen Tai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Shih-Cheng Yang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Keng-Liang Wu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Hsing-Ming Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Chih-Chien Yao
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Cheng-En Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Yao-Kuang Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung 833, Taiwan
| | - Jiunn-Wei Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung 833, Taiwan
| | - Chih-Fang Huang
- Division of Family Physicians, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung 833, Taiwan
| | - Seng-Kee Chuah
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | | |
Collapse
|
|
16
|
Li MJ, Li Q, Sun M, Liu LQ. Comparative effectiveness and acceptability of the FDA-licensed proton pump inhibitors for erosive esophagitis: A PRISMA-compliant network meta-analysis. Medicine (Baltimore) 2017; 96:e8120. [PMID: 28953640 PMCID: PMC5626283 DOI: 10.1097/md.0000000000008120] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 08/17/2017] [Accepted: 09/01/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND This study compared the effectiveness and acceptability of all Food and Drug Administration (FDA)-recommended dose proton pump inhibitors (PPIs) in erosive esophagitis (EE): Dexlansoprazole 60 mg, Esomeprazole 40 mg, Esomeprazole 20 mg, Pantoprazole 40 mg, Lansoprazole 30 mg, Rabeprazole 20 mg, Omeprazole 20 mg. METHODS A systematic literature search was performed using PubMed, Embase, and Cochrane Library. Totally, 25 randomized controlled trials (RCTs) met study selection criteria and were incorporated in this network meta-analysis (NMA) study. RESULTS For the NMA, eligible RCTs of adults with EE verified by endoscopic examination were randomly assigned to the licensed PPIs at least 4 weeks of continuous therapy. The primary efficacy outcome was the endoscopic healing rates at 4 and 8 weeks. Heartburn relief rates were a secondary efficacy outcome. The rates of withdrawal were analyzed as a safety outcome. In comparison to the common comparator omeprazole 20 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [odds ratio (OR), 1.46 (95% confidence interval, 95% CI, 1.24-1.71)] and 8 weeks [1.58 (1.29-1.92)], and improved the heartburn relief rates [1.29 (1.07-1.56)]. In comparison to lansoprazole 30 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [1.30 (1.10-1.53)] and 8 weeks [1.37 (1.13-1.67)], and improved the heartburn relief rates [1.29 (1.03-1.62)]. In terms of acceptability, only dexlansoprazole 60 mg had significantly more all-cause discontinuation than omeprazole 20 mg [1.54 (1.03-2.29)], pantoprazole 40 mg [1.68 (1.08-2.63)], and lansoprazole 30 mg [1.38 (1.02-1.88)]. CONCLUSION The standard-dose esomeprazole 40 mg had more superiority in mucosal erosion healing and heartburn relief. Esomeprazole 40 mg, pantoprazole 40 mg, esomeprazole 20 mg, and lansoprazole 30 mg showed more benefits in effectiveness and acceptability than other interventions.
Collapse
Affiliation(s)
- Mei-Juan Li
- School of Pharmacy, Shanxi Medical University
| | - Qing Li
- Department of Pharmacy, The First Hospital of Shanxi Medical University, Taiyuan
| | - Min Sun
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan
- Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, P.R. China
| | - Li-Qin Liu
- School of Pharmacy, Shanxi Medical University
| |
Collapse
|
|
17
|
Dexlansoprazole for Heartburn Relief in Adolescents with Symptomatic, Nonerosive Gastro-esophageal Reflux Disease. Dig Dis Sci 2017; 62:3059-3068. [PMID: 28916953 PMCID: PMC5649596 DOI: 10.1007/s10620-017-4743-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 08/30/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND Proton pump inhibitors are commonly used to treat gastro-esophageal reflux disease (GERD) and nonerosive GERD (NERD) in adolescents and adults. Despite the efficacy of available medications, many patients have persisting symptoms, indicating a need for more effective agents. AIMS To assess the safety and efficacy of dexlansoprazole dual delayed-release capsules in adolescents for treatment of symptomatic NERD. METHODS A phase 2, open-label, multicenter study was conducted in adolescents aged 12-17 years. After a 21-day screening period, adolescents with endoscopically confirmed NERD received a daily dose of 30-mg dexlansoprazole for 4 weeks. The primary endpoint was treatment-emergent adverse events (TEAEs) experienced by ≥5% of patients. The secondary endpoint was the percentage of days with neither daytime nor nighttime heartburn. Heartburn symptoms and severity were recorded daily in patient electronic diaries and independently assessed by the investigator, along with patient-reported quality of life, at the beginning and end of the study. RESULTS Diarrhea and headache were the only TEAEs reported by ≥5% of patients. Dexlansoprazole-treated patients (N = 104) reported a median 47.3% of days with neither daytime nor nighttime heartburn. Symptoms such as epigastric pain, acid regurgitation, and heartburn improved in severity for 73-80% of patients. Pediatric Gastroesophageal Symptom and Quality of Life Questionnaire-Adolescents-Short Form symptom and impact subscale scores (scaled 1-5) each decreased by an average of 0.7 units at week 4. CONCLUSIONS Use of 30-mg dexlansoprazole in adolescent NERD was generally well tolerated and had beneficial effects on improving heartburn symptoms and quality of life. TRIAL REGISTRATION This study has the ClinicalTrials.gov identifier NCT01642602.
Collapse
|
|
18
|
Inatomi N, Matsukawa J, Sakurai Y, Otake K. Potassium-competitive acid blockers: Advanced therapeutic option for acid-related diseases. Pharmacol Ther 2016; 168:12-22. [PMID: 27514776 DOI: 10.1016/j.pharmthera.2016.08.001] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Accepted: 07/29/2016] [Indexed: 02/07/2023]
Abstract
Acid-related diseases (ARDs), such as peptic ulcers and gastroesophageal reflux disease, represent a major health-care concern. Some major milestones in our understanding of gastric acid secretion and ARD treatment reached during the last 50years include 1) discovery of histamine H2-receptors and development of H2-receptor antagonists, 2) identification of H+,K+-ATPase as the parietal cell proton pump and development of proton pump inhibitors (PPIs), and 3) identification of Helicobacter pylori (H. pylori) as the major cause of peptic ulcers and development of effective eradication regimens. Although PPI treatments have been effective and successful, there are limitations to their efficacy and usage, i.e. short half-life, insufficient acid suppression, slow onset of action, and large variation in efficacy among patients due to CYP2C19 metabolism. Potassium-competitive acid blockers (P-CABs) inhibit H+,K+-ATPase in a reversible and K+-competitive manner, and exhibit almost complete inhibition of gastric acid secretion from the first dose. Many pharmaceutical companies have tried to develop P-CABs, but most of their clinical development has been discontinued due to safety concerns or a similar efficacy to PPIs. Revaprazan was developed in Korea and was the first P-CAB approved for sale. Vonoprazan, approved in 2014 in Japan, has a completely different chemical structure and higher pKa value compared to other P-CABs, and exhibits rapid onset of action and prolonged control of intragastric acidity. Vonoprazan is an effective treatment for ARDs that is especially effective in healing reflux esophagitis and for H. pylori eradication. P-CABs, such as vonoprazan, promise to further improve the management of ARDs.
Collapse
Affiliation(s)
- Nobuhiro Inatomi
- Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251-8555, Japan
| | - Jun Matsukawa
- Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251-8555, Japan.
| | - Yuuichi Sakurai
- Japan Development Center, Takeda Pharmaceutical Company Limited, Chuo-ku, Osaka 540-8645, Japan
| | - Kazuyoshi Otake
- Global Medical Affairs Japan Department, Takeda Pharmaceutical Company Limited, Chuo-ku, Tokyo 103-8668, Japan
| |
Collapse
|
|
19
|
Goh KL, Choi MG, Hsu PI, Chun HJ, Mahachai V, Kachintorn U, Leelakusolvong S, Kim N, Rani AA, Wong BCY, Wu J, Chiu CT, Shetty V, Bocobo JC, Chan MM, Lin JT. Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor - Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region. J Neurogastroenterol Motil 2016; 22:355-366. [PMID: 26932927 PMCID: PMC4930293 DOI: 10.5056/jnm15150] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2015] [Revised: 01/27/2016] [Accepted: 01/30/2016] [Indexed: 12/13/2022] Open
Abstract
Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia.
Collapse
Affiliation(s)
- Khean Lee Goh
- Department of Medicine, University of Malaya, Kuala Lumpur,
Malaysia
| | - Myung Gyu Choi
- Department of Internal Medicine, Catholic University of Korea, Seoul,
Korea
| | - Ping I Hsu
- Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung,
Taiwan ROC
| | - Hoon Jai Chun
- Department of Internal Medicine, Korea University College of Medicine, Seoul,
Korea
| | - Varocha Mahachai
- Division of Gastroenterology, Chulalongkorn University, Bangkok,
Thailand
| | - Udom Kachintorn
- Division of Gastroenterology, Department of Internal Medicine, Siriraj Hospital, Mahidol University, Bangkok,
Thailand
| | - Somchai Leelakusolvong
- Division of Gastroenterology, Department of Internal Medicine, Siriraj Hospital, Mahidol University, Bangkok,
Thailand
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do,
Korea
| | - Abdul Aziz Rani
- Department of Internal Medicine, University of Indonesia, Depok,
Indonesia
| | - Benjamin C Y Wong
- Department of Medicine, The University of Hong Kong, Hong Kong SAR,
China
| | - Justin Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR,
China
| | - Cheng Tang Chiu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital & Chang Gung University, Taoyuan,
Taiwan ROC
| | - Vikram Shetty
- Medical Affairs, Takeda Pharmaceuticals (Asia Pacific) Pte Ltd,
Singapore
| | - Joseph C Bocobo
- St. Luke’s College of Medicine-William H. Quasha Memorial, Quezon City,
Philippines
| | - Melchor M Chan
- Faculty of Medicine and Surgery, University of Santo Tomas Hospital, Manila,
Philippines
| | - Jaw-Town Lin
- Department of Medicine, Fu Jen Catholic University, New Taipei City,
Taiwan ROC
| |
Collapse
|
|
20
|
Mermelstein J, Mermelstein AC, Chait MM. Proton pump inhibitors for the treatment of patients with erosive esophagitis and gastroesophageal reflux disease: current evidence and safety of dexlansoprazole. Clin Exp Gastroenterol 2016; 9:163-72. [PMID: 27471402 PMCID: PMC4948703 DOI: 10.2147/ceg.s91602] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Gastroesophageal reflux disease is the most common upper gastroenterology disorder in the US. It is associated with a variety of complications and significantly impacts quality of life. Proton pump inhibitors are the most effective treatment. Dexlansoprazole modified release (MR) is a proton pump inhibitor that employs a novel release formulation that prolongs its absorption and allows for more flexibility in dosing. Dexlansoprazole MR can be dosed without regard to food intake or time of day, and once-daily dosing may replace twice-daily dosing of other agents. Dexlansoprazole MR is effective for healing and maintenance of erosive esophagitis, and for the treatment of nonerosive disease, including nocturnal gastroesophageal reflux disease. Dexlansoprazole MR is safe and well tolerated, and can improve quality of life.
Collapse
Affiliation(s)
- Joseph Mermelstein
- Department of Medicine, Mount Sinai Beth Israel/Icahn School of Medicine
| | | | - Maxwell M Chait
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
| |
Collapse
|
|
21
|
Wu DC, Kuo CH, Tsay FW, Hsu WH, Chen A, Hsu PI. A Pilot Randomized Controlled Study of Dexlansoprazole MR-Based Triple Therapy for Helicobacter Pylori Infection. Medicine (Baltimore) 2016; 95:e2698. [PMID: 26986096 PMCID: PMC4839877 DOI: 10.1097/md.0000000000002698] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 01/10/2016] [Accepted: 01/14/2016] [Indexed: 02/07/2023] Open
Abstract
Dexlansoprazole MR is the R-enantiomer of lansoprazole that is delivered by a dual delayed release formulation. It is effective for symptom control of patients with gastroesophageal reflux disease. However, its efficacy in the treatment of Helicobacter pylori infection remains unclear. This pilot, randomized, controlled, head-to-head study was conducted to investigate whether the efficacy of single-dose dexlansoprazole MR-based triple therapy was noninferior to double-dose rabeprazole-based triple therapy in the treatment of H pylori infection. Consecutive H pylori-infected subjects were randomly allocated to either 7-day dexlansoprazole MR-based standard triple therapy (dexlansoprazole MR 60 mg once daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily) or rabeprazole-based triple therapy (rabeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily). H pylori status was assessed 6 weeks after the end of treatment. A total of 177 H pylori-infected patients were randomized to receive dexlansoprazole MR-based (n = 90) or rabeprazole-based (n = 87) triple therapy. Intention-to-treat analysis demonstrated no differences between eradication rates of the 2 study groups (83.3% vs 81.6%; P = 0.736). Per-protocol analysis yielded comparable results (85.1% vs 81.2%; P = 0.497). Both groups exhibited similar frequencies of adverse events (7.8% vs 4.6%; P = 0.536) and drug compliance (98.9% vs 97.7%; P = 0.496). Multivariate analysis disclosed that the presence of clarithromycin resistance was the only independent factors predictive of treatment failure with an odds ratio of 6.8 (95% confidence interval: 1.2-37.6). This work demonstrates that single-dose dexlansoprazole MR-based triple therapy yields a similar eradication rate as double-dose rabeprazole-based therapy. Since the pharmaceutical cost of the single-dose dexlansoprazole MR regime is lower than that of the double-dose rabeprazole regimen, dexlansoprazole-based therapy can reasonably be recommended in the first-line treatment of H pylori infection.
Collapse
Affiliation(s)
- Deng-Chyang Wu
- From the Division of Gastroenterology (D-CW, W-HH), Department of Internal Medicine, Kaohsiung Medical University Hospital; Division of Internal Medicine (D-CW), Kaohsiung Municipal Ta-Tung Hospital; Department of Internal Medicine and Cancer Center (D-CW), Kaohsiung Medical University Hospital; Cancer for Stem Cell Research (D-CW), Kaohsiung Medical University; Division of Gastroenterology (F-WT, P-IH), Kaohsiung Veterans General Hospital and National Yang-Ming University; and Institute of Biomedical Sciences (AC), National Sun Yat-Sen University, Kaohsiung, Taiwan
| | | | | | | | | | | |
Collapse
|
|
22
|
Dexlansoprazole - a new-generation proton pump inhibitor. GASTROENTEROLOGY REVIEW 2015; 10:191-6. [PMID: 26759624 PMCID: PMC4697039 DOI: 10.5114/pg.2015.56109] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 11/30/2015] [Accepted: 12/04/2015] [Indexed: 12/13/2022]
Abstract
Dexlansoprazole modified release (MR) is an R-enantiomer of lansoprazole and a new-generation proton pump inhibitor exhibiting high efficacy in the treatment of symptoms and lesions associated with erosive oesophagitis caused by gastroesophageal reflux disease (GERD). The dual release of the active ingredient - in the duodenum and the small intestine - makes it possible to achieve two peak concentrations at various times, within two and five hours of administration. Dexlansoprazole MR ensures the longest maintenance of drug concentration in the plasma of all known proton pump inhibitors, and the longest proton pump inhibitory effect. The basic indications for the drug include all forms of gastroesophageal reflux disease, especially with night-time heartburn and sleep disorders resulting from GERD. Dexlansoprazole can be taken regardless of meal times. It has a good safety profile and carries a low risk of adverse interactions with other drugs.
Collapse
|
|
23
|
Frye JW, Peura DA. Managing gastroesophageal reflux disease - comparative efficacy and outcomes of dexlansoprazole MR. Ther Clin Risk Manag 2015; 11:1649-56. [PMID: 26586949 PMCID: PMC4634831 DOI: 10.2147/tcrm.s66680] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
The management of gastroesophageal reflux disease (GERD) has been revolutionized with the development of proton pump inhibitors (PPIs). Unfortunately, due to the inherent pharmacokinetic and pharmacodynamic profiles of conventional PPIs, many patients continue to suffer from symptoms related to GERD despite appropriate use of PPIs. Dexlansoprazole MR is a PPI with a unique dual delayed-release delivery system that has been designed to address the unmet needs in GERD management. Specifically, dexlansoprazole MR addresses limitations with short plasma half-life and need for meal-associated dosing, characteristic of conventional PPIs. In addition, dexlansoprazole MR has been shown to be effective in several specific clinical situations. These include coadministration with clopidogrel, healing of all grades of erosive esophagitis, improvement in reflux-related quality of life, step down to once-per-day dosing, and treatment of Helicobacter pylori infections. Furthermore, dexlansoprazole MR has been found to induce symptom improvement in patients with nonerosive esophageal reflux disease, nocturnal heartburn and GERD-related sleep disturbance, and regurgitation. Overall, dexlansoprazole MR is a unique and useful tool in the management of GERD.
Collapse
Affiliation(s)
- Jeanetta W Frye
- Division of Gastroenterology and Hepatology, University of Virginia Health Sciences Center, Charlottesville, VA, USA
| | - David A Peura
- Division of Gastroenterology and Hepatology, University of Virginia Health Sciences Center, Charlottesville, VA, USA
| |
Collapse
|
|
24
|
Sun L, Cao Y, Jiao H, Fang Y, Yang Z, Bian M, Zhang H, Gong X, Wang Y. Enantioselective determination of (R
)- and (S
)-lansoprazole in human plasma by chiral liquid chromatography with mass spectrometry and its application to a stereoselective pharmacokinetic study. J Sep Sci 2015; 38:3696-703. [PMID: 26333119 DOI: 10.1002/jssc.201500653] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 08/10/2015] [Accepted: 08/18/2015] [Indexed: 11/07/2022]
Affiliation(s)
- Luning Sun
- Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Yang Cao
- Department of Gastroenterology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Huiwen Jiao
- Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Yunqian Fang
- Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Zhicheng Yang
- Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Mingliang Bian
- Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Hongwen Zhang
- Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Xiaojian Gong
- Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Yongqing Wang
- Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
25
|
Advances in the evaluation and management of esophageal disease of systemic sclerosis. Curr Rheumatol Rep 2015; 17:475. [PMID: 25475597 DOI: 10.1007/s11926-014-0475-y] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Symptoms of heartburn and dysphagia as well as objective findings of abnormal esophageal acid exposure and esophageal dysmotility are common in patients with systemic sclerosis (SSc). Treatments for SSc esophageal disease are generally limited to gastroesophageal reflux disease (GERD) treatment with proton pump inhibitors. Progresses made in esophageal diagnostic testing offer the potential for improved clinical characterization of esophageal disease in SSc that may help direct management decisions. In addition to reviewing GERD management in patients with SSc, present and potential uses of endoscopy, reflux monitoring, manometry, impedance planimetry, and endoscopic ultrasound are discussed.
Collapse
|
|
26
|
Wu MS, Tan SC, Xiong T. Indirect comparison of randomised controlled trials: comparative efficacy of dexlansoprazole vs. esomeprazole in the treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2013; 38:190-201. [PMID: 23718547 DOI: 10.1111/apt.12349] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Revised: 04/16/2013] [Accepted: 05/07/2013] [Indexed: 12/24/2022]
Abstract
BACKGROUND Dexlansoprazole is a new proton pump inhibitor (PPI) with a dual delayed-release system. Both dexlansoprazole and esomeprazole are an enantiomer of lansoprazole and omeprazole respectively. However, there is no head-to-head trial data or indirect comparison analyses between dexlansoprazole and esomeprazole. AIM To compare the efficacy of dexlansoprazole with esomeprazole in healing erosive oesophagitis (EO), the maintenance of healed EO and the treatment of non-erosive reflux disease (NERD). METHODS Randomised Controlled Trials (RCTs) comparing dexlansoprazole or esomeprazole with either placebo or another PPI were systematically reviewed. Random-effect meta-analyses and adjusted indirect comparisons were conducted to compare the treatment effect of dexlansoprazole and esomeprazole using a common comparator. The relative risk (RR) and 95% confidence interval (CI) were calculated. RESULTS The indirect comparisons revealed significant differences in symptom control of heartburn in patients with NERD at 4 weeks. Dexlansoprazole 30 mg was more effective than esomeprazole 20 mg or 40 mg (RR: 2.01, 95% CI: 1.15-3.51; RR: 2.17, 95% CI: 1.39-3.38). However, there were no statistically significant differences between the two drugs in EO healing and maintenance of healed EO. Comparison of symptom control in healed EO was not able to be made due to different definitions used in the RCTs. CONCLUSIONS Adjusted indirect comparisons based on currently available RCT data suggested significantly better treatment effect in symptom control of heartburn in patients with NERD for dexlansoprazole against esomeprazole. No statistically significant differences were found in other EO outcomes. However, these study findings need to be interpreted with caution due to small number of studies and other limitations.
Collapse
Affiliation(s)
- M S Wu
- Department of Internal Medicine, Taiwan National University, Taipei, Taiwan
| | | | | |
Collapse
|
|
27
|
Shin JM, Kim N. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors. J Neurogastroenterol Motil 2013; 19:25-35. [PMID: 23350044 PMCID: PMC3548122 DOI: 10.5056/jnm.2013.19.1.25] [Citation(s) in RCA: 270] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Revised: 12/20/2012] [Accepted: 12/21/2012] [Indexed: 12/13/2022] Open
Abstract
Proton pump inhibitor (PPI) is a prodrug which is activated by acid. Activated PPI binds covalently to the gastric H+, K+-ATPase via disulfide bond. Cys813 is the primary site responsible for the inhibition of acid pump enzyme, where PPIs bind. Omeprazole was the first PPI introduced in market, followed by pantoprazole, lansoprazole and rabeprazole. Though these PPIs share the core structures benzimidazole and pyridine, their pharmacokinetics and pharmacodynamics are a little different. Several factors must be considered in understanding the pharmacodynamics of PPIs, including: accumulation of PPI in the parietal cell, the proportion of the pump enzyme located at the canaliculus, de novo synthesis of new pump enzyme, metabolism of PPI, amounts of covalent binding of PPI in the parietal cell, and the stability of PPI binding. PPIs have about 1hour of elimination half-life. Area under the plasmic concentration curve and the intragastric pH profile are very good indicators for evaluating PPI efficacy. Though CYP2C19 and CYP3A4 polymorphism are major components of PPI metabolism, the pharmacokinetics and pharmacodynamics of racemic mixture of PPIs depend on the CYP2C19 genotype status. S-omeprazole is relatively insensitive to CYP2C19, so better control of the intragastric pH is achieved. Similarly, R-lansoprazole was developed in order to increase the drug activity. Delayed-release formulation resulted in a longer duration of effective concentration of R-lansoprazole in blood, in addition to metabolic advantage. Thus, dexlansoprazole showed best control of the intragastric pH among the present PPIs. Overall, PPIs made significant progress in the management of acid-related diseases and improved health-related quality of life.
Collapse
|
|
28
|
Altan E, Blondeau K, Pauwels A, Farré R, Tack J. Evolving pharmacological approaches in gastroesophageal reflux disease. Expert Opin Emerg Drugs 2012; 17:347-59. [PMID: 22834684 DOI: 10.1517/14728214.2012.702753] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) have considerably improved quality of life in patients with gastroesophageal reflux disease (GERD). However, many patients remain symptomatic despite standard PPI therapy. AREAS COVERED This review focuses on evolving therapeutic strategies related to the pathophysiological processes of GERD and insufficient response to PPIs. Several clinical trials evaluated new PPI formulations and newer types of acid-suppressive drugs. These studies have evaluated traditional end points in GERD, but have not shown clinical superiority to current PPIs. Novel therapeutic strategies targeting underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxations (TLESRs) and esophageal hypersensitivity, are being developed for add-on therapy to PPIs. Prokinetic drugs may also have some potential in the add-on treatment of GERD with insufficient response to PPIs. Add-on studies are hampered by insufficient information on optimal patient selection and lack of established end points. EXPERT OPINION Newer drugs for symptomatic control in GERD have largely focused on improved acid suppression, without evidence of clinical superiority. Drugs targeting esophageal motility and sensitivity to be used as add-onc therapy in PPI insufficient responders have not reached Phase III trials to date, due to difficulties with patient selection, tolerability and end points.
Collapse
Affiliation(s)
- Ege Altan
- University of Leuven, Translational Research Center for Gastrointestinal Disorders, Herestraat 49, B-3000, Leuven, Belgium
| | | | | | | | | |
Collapse
|